Abstract：
Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-β. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.
摘要：
已经开发了癌症免疫疗法以通过激活干扰素基因的先天免疫刺激因子（STING）途径来改善患者的治疗效果。然而,大多数患者无法从这种疗法中受益，主要是由于免疫反应过低和缺乏肿瘤特异性的问题。在这里，我们通过开发用于STING激动剂的黑磷量子点（BPQD）的双功能平台来报告这两个问题的解决方案。具体来说,BPQD可以连接目标官能团并通过配位金属离子来调节表面ζ电位以增加负载(超过5倍),同时保持高普遍性(7个STING激动剂)。STING激动剂的受控释放使其与蛋白质的特异性相互作用，通过磷酸化TBK1和IFN-IRF3并分泌高水平的免疫刺激细胞因子来激活STING途径并刺激免疫抑制因子的分泌释放，包括IL-6，IFN-α，和IFN-β。此外，免疫疗法增强了BPQDs平台的轻度光热疗法（PTT），产生足够的T细胞以消除肿瘤并防止肿瘤复发。这项工作有助于进一步研究小分子免疫药物的靶向递送，以促进临床免疫治疗的发展。
